medwireNews: US researchers question the benefits of using a gene expression classifier (GEC) in patients with cytologically indeterminate thyroid nodules.

The commercial GEC test, which measures RNA transcripts from 167 genes, was performed alongside standard cytopathology, clinical, laboratory and radiological assessments in 273 patients attending hospital for a thyroid nodule, averaging 2.4 cm in diameter, between 2012 and 2014.

Test results were suspected of being malignant in 85.3% of cases, while 11.4% of nodules were considered benign and 2.9% indeterminate.

A suspicious GEC result led to a change in the clinical treatment plan of just 23 (8.4%) patients and 16 of these patients were later found to be “inappropriately overtreated relative to postoperative histopathology analysis”, report Ralph Tufano, from The Johns Hopkins University School of Medicine in Baltimore, Maryland, and co-workers.

This included four out of five patients who had no clinical indication for GEC testing but whose surgeon recommended total thyroidectomy instead of hemithyroidectomy on the basis of GEC results, they add.

The GEC test was 96.7% sensitive for malignancy but had a specificity of just 14.7%, giving positive and negative predictive values of 44.4% and 86.3%, respectively. The corresponding positive and negative predictive value for Bethesda category III and IV indeterminate nodules were 42.1% and 83.3%.

Finding this Bethesda negative predictive value to be lower than previously reported, the researchers say this finding “calls into question the performance of the test when applied to a patient seeking surgical consultation in a specialized thyroid surgery center”.

The authors therefore conclude in JAMA Otolaryngology–Head & Neck Surgery that “clinicians must continue to follow the current management strategies of nodular thyroid disease instead of only relying on any single diagnostic test”.

They add: “Since the field of diagnostic molecular testing is new and advances are regularly occurring, clinicians need to stay informed of continued research and advances made in the field that may change the understanding of how best to use molecular markers in a clinical setting.”